The overall objectives of the program are to improve the ratio of beneficial to adverse effects of drugs via basic research and clinical investigation. Principal approaches to this objective are two: (1) improvement in design and early development of drugs through increased knowledge of cellular uptake, subcellular mechanisms of action and relation to metabolic processes; (2) improvement in use of current drugs through increased knowledge of their fate in vivo; their effects and factors influencing these. Among the projects within this broad program are development of new radioactive imaging agents for myocardium, and their study in heart disease; characterization of uptake processes for analgesic and other CNS-active drugs by blood cells and nervous tissue; investigation of drug effects on mechanisms controlling hormonal secretion; quantitation of breakdown and repair of connective tissue, by measuring urinary glycosyl amino acids, and study of drug effects on these processes; studies of the practical aspects (bioavailability of various preparations of drugs) and theoretical basis (mechanism of absorption of acidic and basic drugs) of gastrointestinal absorption of drugs; improved use of corticosteroid drugs to prevent acute rejection of transplants; studies of the relation between vascular lesions of the central nervous system and reactivity of the heart to cardiac glycosides.